Hepatic necrosis and hemorrhage following hyperthermic intraperitoneal chemotherapy with oxaliplatin: A review of two cases.

Cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is now becoming a standard of care for peritoneal carcinomatosis (PC) in selected patients. Eradication of macroscopic disease (nodules > 2.5 mm) is realized through meticulous CS. Following CS, intraperitoneal chemotherapy is administered to treat microscopic disease (1). An increasing number of patients presenting with PC arising from colorectal cancer (2),(3), pseudomyxoma peritonei (4), and malignant peritoneal mesothelioma (5) have been treated using this combined modality with promising results. However, this procedure is associated with significant morbidity. Major complication rates reach 52% in some series (6). Sepsis, abscesses, anastomotic leaks, thromboembolic events, haematological toxicity and renal insufficiency are the main complications described in literature (6). We herein report two unusual cases of hemorrhagic shock with hemoperitoneum associated with severe hepatic necrosis following CS and HIPEC with oxaliplatin (HIPEC-OX). Over 75 HIPEC-OX have been performed in the past five years in our center. HIPEC is performed with the abdomen open using the Coliseum technique, with skin edges retracted above the surface of the abdomen on a metallic ring. Chemotherapy solution (oxaliplatin 460mg/m(2) diluted in a 2L/m(2) volume of D5%W) is delivered in a continuous closed circuit using four 36-French drains (two inlets and two outlets) connected to two pumps. The flow rate is 1L/min for each pump, and four thermal probes inside the peritoneal cavity give continuous temperature feedback. Intra-abdominal temperature is maintained between 42°C and 44°C and the perfusion duration is 30 minutes. The infusion is then completely evacuated and the abdomen is closed. In our institution, intraperitoneal chemotherapy is not associated with simultaneous intravenous chemotherapy (5-fluorouracile), except for patients with colorectal PC. Various chemotherapeutic agents have been proposed for HIPEC (7). Oxaliplatin, a third generation platinum complex derived from cisplatinum, is a commonly used agent and one of the preferred agent for PC arising from colorectal carcinoma. It has proven activity against colorectal cancer cells and has high intra-tumoral penetration and intra-peritoneal concentration. Moreover, oxaliplatin's cytotoxicity is potentiated by hyperthermia and has a low systemic absorption, with possibly less systemic toxicity (8),(9).